Wednesday, January 27, 2016

Scientists open the ‘black box’ of schizophrenia with dramatic genetic discovery

Every few days, it seems like there is a story of a major scientific "breakthrough" in the news. Yet the reality of science is that most pathways which look promising at first eventually close up or peter out. However, if there are enough potential breakthroughs developed, one or more will eventually prove itself to be useful, either in solving a problem or leading to the right direction were the solution will eventually be found.

For the first time, scientists have pinned down a molecular process in the brain that helps to trigger schizophrenia. The researchers involved in the landmark study, which was published Wednesday in the journal Nature, say the discovery of this new genetic pathway probably reveals what goes wrong neurologically in a young person diagnosed with the devastating disorder. ... The researchers, chiefly from the Broad Institute, Harvard Medical School and Boston Children's Hospital, found that a person's risk of schizophrenia is dramatically increased if they inherit variants of a gene important to "synaptic pruning" -- the healthy reduction during adolescence of brain cell connections that are no longer needed. In patients with schizophrenia, a variation in a single position in the DNA sequence marks too many synapses for removal and that pruning goes out of control. The result is an abnormal loss of gray matter.

This seems to explain for the first time why autopsies of the brains of schizophrenics show a big loss in gray matter -- their DNA is ordering far too much "synaptic pruning."

There have been hundreds of theories about schizophrenia over the years, but one of the enduring mysteries has been how three prominent findings related to each other: the apparent involvement of immune molecules, the disorder's typical onset in late adolescence and early adulthood, and the thinning of gray matter seen in autopsies of patients. "The thing about this result," said McCarroll, the lead author, " it makes a lot of other things understandable. To have a result to connect to these observations and to have a molecule and strong level of genetic evidence from tens of thousands of research participants, I think that combination sets [this study] apart."

Now that scientists seem to know what is going on for the first time, they will need to develop a cure, a way to fix the DNA sequencing in these patients. That might be a long way off:

The study offers a new approach to schizophrenia research, which has been largely stagnant for decades. ... "We now have a strong molecular handle, a pathway and a gene, to develop better models," he said. Which isn't to say a cure is right around the corner. "This is the first exciting clue, maybe even the most important we’ll ever have, but it will be decades" before a true cure is found," Hyman said. "Hope is a wonderful thing. False promise is not."